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Zevalin
Expert review by:
Leo I. Gordon, MD, is the Abby and John Friend Professor of Cancer Research and Professor of Medicine at Northwestern University
in Chicago, IL. He is Chief of the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine and
Associate Director for Clinical Sciences at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.
What is Zevalin?
Zevalin (Ibritumomab tiuxetan) was the first radioimmunotherapy treatment to be approved by the U.S. Food
and Drug Administration (FDA) for the treatment of nonHodgkin lymphoma (NHL). Zevalin has been approved
for the treatment of patients with relapsed or refractory
lowgrade, follicular, or transformed B-cell NHL, including
patients with follicular NHL who are no longer responding
to treatment with Rituxan (rituximab), a monoclonal
antibody therapy.
“Treatment with the Zevalin regimen
can be completed within a week on
an outpatient basis.”
Zevalin is different in many ways from conventional
chemotherapy or external beam radiation therapy. Zevalin
combines the cell targeting ability of a monoclonal antibody
with the additional cell killing ability of a radioactive
particle, or radioisotope, called yttrium-90. Treatment with
the Zevalin regimen can be completed within a week on an
outpatient basis. It is generally well tolerated by patients,
without the hair loss and nausea that often accompany
chemotherapy treatments. The most common side effect is
a temporary reduction in blood cell counts.
“It is generally well tolerated by patients,
without the hair loss and nausea that often
accompany chemotherapy treatments.”
CD 20 Antigen
Corresponding
Binding Site on
antibody
Antibody targeting antigen on cell
What is a Monoclonal Antibody?
Antibodies are normal components of the body’s immune
system that can recognize and destroy foreign invaders
such as bacteria and viruses. Scientists can now produce
monoclonal antibodies designed to recognize very specific
targets, or antigens, that are present on certain kinds of
cancer cells. Rituxan was the first monoclonal antibody to
receive FDA approval.
Therapy with a monoclonal antibody is an effective way
of specifically targeting certain kinds of cancer cells, with
a low degree of toxicity to normal cells. Monoclonal
antibody therapy is administered by intravenous infusion,
generally on an outpatient basis. Once in the bloodstream,
monoclonal antibodies travel throughout the body and
bind themselves to cells that have the specific target antigen,
such as cancer cells. This activity alerts the body’s own
immune system to recognize and help destroy the bound
cells. Although some normal cells that also have the specific
target antigen may be affected, the body can replace these
normal cells following treatment.
The monoclonal antibody used in the Zevalin regimen specifically recognizes and attaches to the CD20 antigen, which
is found on the surface of lymphocytes, including the cancer
cells in patients with B-cell NHL.
What is Radioimmunotherapy?
Radioimmunotherapy is a cancer therapy, involving the
combination of a monoclonal antibody with a radioisotope, as a source of radiation. When a monoclonal antibody is combined with a radioisotope, it is said to be ‘radiolabeled.’ With radioimmunotherapy, the radiolabeled
antibody targets and binds to a specific antigen present on
cancer cells, delivering a dose of radiation directly to them.
Not only does the radiation destroy the cell to which the
antibody is bound, but it also destroys the surrounding
cells, in what is called the “crossfire” effect.
indium-111 Zevalin is very small, and patients do not need
to observe any special safety precautions following this
part of the regimen.
For treatment, Zevalin is combined with the yttrium-90
radioisotope, a pure beta emitter. The radiation from the
therapeutic dose of yttrium-90 Zevalin is strong enough to
damage and kill the targeted cancer cells and nearby cells,
including some normal cells.
“In clinical trials involving patients with
low-grade non-Hodgkin lymphoma,
the reported response rates to Zevalin
have been 70 percent to 80 percent.”
How is Zevalin given?
Radiolabeled antibody killing off malignant cells
Products are currently on the market for
Radioimmunotherapy?
There are two products currently approved by the FDA for
radioimmunotherapy of patients with B-cell lymphomas:
Zevalin and Bexxar. Both use radioactively-labeled mouse
monoclonal antibodies targeting the CD20 antigen.
What are the differences between
Zevalin and Bexxar?
Bexxar employs Iodine-131, a radiation-emitting form of
iodine, attached to the monoclonal antibody tositumomab.
Tositumomab seeks out and binds to CD20, found on the
surface of B-cells. Once it is combined with lodine-131,
tositumomab is able to deliver its radiation to targeted
cells. lodine-131 emits beta and gamma radiation. Beta
radiation is responsible for most of the tumorkilling
effect. Gamma radiation allows gamma camera scans to
evaluate the distribution and clearance of radiation from
the patient’s body. Iodine-131 radiation is eliminated from
the body mainly through the urine and by the natural
decay of lodine-131 (please see LRF’s Bexxar fact sheet for
more information). The Zevalin regimen uses two different
radioisotopes, indium- 111 and yttrium-90. Indium-111
radiolabeled Zevalin is used for imaging studies. The
amount of radiation associated with this imaging dose of
The Zevalin regimen is delivered over the course of about
a week on an outpatient basis. Delivery of the regimen is
coordinated by a team of healthcare professionals, including
oncologists, nuclear medicine physicians or radiation
oncologists, nurses, pharmacists and technicians. Because
the Zevalin regimen involves the use of radioisotopes, it
is necessary to involve persons specially trained in the safe
handling of these substances at a licensed nuclear medicine
or radiation oncology facility.
On day one of the regimen, the patient first receives an
intravenous infusion of Rituxan, which takes a few hours.
Following the Rituxan infusion, the patient will go to a
nuclear medicine or radiation oncology facility to receive
an imaging dose of indium-111 Zevalin. This intravenous
infusion will take approximately 10 minutes. A nurse or
technician will stay with the patient during treatment.
On day one or day two, whole body images will be taken
with a gamma camera. Then, on day two or day three, additional images will be taken. The physician may recommend that additional images be taken on day four or five,
between 90 to 120 hours after the infusion of indium-111
Zevalin. The physician uses these images to view the path
of indium-111 Zevalin in the body.
Approximately one week after the initial treatment day,
the patient will return for a second infusion of Rituxan
followed by yttrium-90 Zevalin, the therapeutic portion of
the Zevalin regimen. After receiving Rituxan, the patient
will again go to the nuclear medicine or radiation oncology
facility, this time to receive yttrium-90 Zevalin. Yttrium-90
Zevalin is administered by an intravenous infusion that is
completed in about 10 minutes. Imaging studies are not
necessary after this infusion.
What precautions are necessary after
receiving yttrium-90 Zevalin?
Radiation from yttrium-90 Zevalin does not escape
outside the body, but a small amount of radiation may be
present (for about a week following treatment) in body
fluids, such as blood and urine. Minimal radiation safety
precautions are required. Patients should wash their hands
thoroughly after urination and use a condom during sexual
intercourse. In general, it is not necessary to avoid contact
with friends or family during this time and isolation is not
required. Patients can usually return to work and their usual
activities following treatment. Patients should speak with
their physician regarding recommended safety precautions
and any questions or concerns that they may have.
What side effects are associated
with Zevalin?
Because the Zevalin regimen involves the administration of
Rituxan, side effects of Rituxan and Zevalin are discussed.
The most common side effects associated with Rituxan
are mild, flu-like symptoms. Physicians will often provide
medications such as Tylenol and Benadryl to manage these
temporary side effects.
The administration of yttrium-90 Zevalin usually results
in no infusion-related toxicities. However, because of the
radioactivity of this treatment, blood cell counts will be
lowered. The period of lowered blood cell counts generally
occurs 4 to 6 weeks following therapy, with recovery
of counts 2 to 3 weeks later. It is important to note that
Zevalin is not associated with hair loss or with the nausea
and vomiting typically seen with chemotherapy.
Who is a candidate for Zevalin?
Zevalin has been approved for the treatment of patients with
relapsed or refractory B-cell lymphomas of the following
subtypes: low-grade and/or follicular, or transformed B-cell
NHL, including patients who are no longer responding to
Rituxan treatment. Zevalin is not currently recommended
for patients with greater than 25 percent bone marrow
involvement, impaired bone marrow reserve or for patients
with platelet counts less than 100,000.
How effective is Zevalin?
In clinical trials involving patients with low-grade NHL,
the reported response rates to Zevalin have been 70 percent
to 80 percent. Zevalin produced responses in patients who
were no longer responding to treatment with chemotherapy,
were no longer responding to treatment with Rituxan, and
those who had bulky disease.
“Importantly, there are patients who are still
in remission over 5 years after treatment
with a single dose of Zevalin.”
In a randomized Phase III clinical trial for patients with
relapsed and refractory indolent lymphoma, comparing
Rituxan and Zevalin treatments, 50 percent of patients
responded to Rituxan and 80 percent of patients responded
to Zevalin. The patients who were treated with Zevalin
had a complete response rate of 30 percent, compared to
20 percent of Rituxan patients. Patients had a median age
of 60, with an average of two prior therapies. The median
duration of response was 13.9 months with Zevalin
compared to 11.8 months with Rituxan. The subgroup of
patients with follicular lymphoma had a median duration
of response of 16.7 months. Importantly, there are patients
who are still in remission over 5 years after treatment with
a single dose of Zevalin.
Does Zevalin therapy “burn ridges” for future
treatments with other products?
It is not believed that Zevalin will limit future treatment
options. Data reported that NHL treatments such as
chemotherapy, Rituxan, radiation therapy and stem cell
transplant are all feasible following Zevalin therapy.
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©2008 Lymphoma Research Foundation
Getting the Facts is published by the Lymphoma
Research Foundation for the purpose of informing
and educating readers. Because each person’s body
and response to treatment is different, no individual
should self-diagnose or embark upon any course
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Last Updated March 2008
For more information about Zevalin,
please consult Zevalin Prescribing Information,
call 1- 866-298-8433, visit www.zevalin.com
or speak with your physician.